First Author | Choi P | Year | 2013 |
Journal | J Pediatr Surg | Volume | 48 |
Issue | 6 | Pages | 1340-7 |
PubMed ID | 23845628 | Mgi Jnum | J:308055 |
Mgi Id | MGI:6725717 | Doi | 10.1016/j.jpedsurg.2013.03.042 |
Citation | Choi P, et al. (2013) IGF-2 mediates intestinal mucosal hyperplasia in retinoblastoma protein (Rb)-deficient mice. J Pediatr Surg 48(6):1340-7 |
abstractText | PURPOSE: We have previously demonstrated a hyperplastic phenotype when Rb expression was disrupted within the intestinal epithelium. These findings mimic resection-induced adaptation suggesting a possible mechanistic role for Rb during adaptation. The purpose of the present study was to elucidate a mechanism for how Rb deficiency induces intestinal hyperplasia. METHODS: Enterocytes isolated from intestine-specific Rb knockout mice (Rb-IKO) underwent a microarray to elucidate their gene expression profile. IGF2 expression was significantly elevated, which was subsequently confirmed by RT-PCR and in situ mRNA hybridization. Mice with deficient expression of IGF2 or its receptor IGF1R were therefore crossed with Rb-IKO mice to determine the significance of IGF2 in mediating the Rb-IKO intestinal phenotype. RESULTS: Expression of IGF2 was significantly elevated in villus enterocytes of Rb-IKO mice. The mucosal hyperplasia in Rb-IKO mice was reversed when either IGF2 or IGF1R expression was genetically disrupted in Rb-IKO mice. CONCLUSION: IGF-2 expression is significantly elevated in villus enterocytes and is required for the hyperplastic intestinal mucosal phenotype of Rb-IKO mice. The trophic effects of IGF2 require intact IGF1R signaling within the intestinal epithelium. These findings reveal novel regulatory roles for Rb in expanding intestinal mucosal surface area. |